Mice overexpressing amyloid precursor protein (APP) and harbouring presenilin-1 (PS1) gene are more susceptible to photothrombotic stroke and post-stroke memory impairment than APP transgenic mice

Abstract

We used Rose Bengal (RB; 1 mg IV at 1 min before illumination for 15 min) to induce photothrombotic stroke in 3-month-old mice overexpressing human APP with or without human mutant PS1 gene. Sham stroke groups received RB without illumination. Regional cerebral blood flow (CBF) over the penumbra was monitored during illumination in 2 groups of mice. Two days after real or sham stroke, sensorimotor functions were assessed prior to determination of infarct volume (IFV) in some groups using triphenyltetrazolium chloride staining. Seven days after real or sham stroke, sensorimotor functions and memory tests were done prior to IFV assessment in other groups. One group of mice received a longer illumination of 20 min and was sacrificed 7 days later. Reduction in CBF during illumination was comparable between the APP and APP/PS1 mice. Two days after stroke, the relative IFV was, in mean±SEM, 6.59±0.87% (n=8) and 8.19±0.82% (n=8) in the APP and APP/PS1 mice, respectively. Compared with the sham stroke group, a significant increase in the time required to turn around inside an alley of similar extent was seen in the transgenic mice at 2 days after stroke; there was no difference in the latency of falling from a pole. Seven days after stroke, the relative infarct volume was similar in both groups of APP mice undergone 15 or 20 min of illumination (5.85±0.94%; n=12), but this was smaller than that of the APP/PS1 transgenic mice (9.15±0.91%; n=6; P<0.01). When compared to the sham stroke groups, there was no difference in the sensorimotor functions, and time spent in the target quadrant of the Morris water maze test was reduced in the APP/PS1 (P<0.05) but not APP transgenic mice. In conclusion, the APP/PS1 double transgenic mice are more susceptible to photothrombotic stroke than the APP transgenic mice with a larger IFV and manifestation of memory impairment.